IL-33 activates group 2 innate lymphoid cell expansion and modulates endometriosis

Abstract

Chronic inflammation and localized alterations in immune cell function are suspected to contribute to the progression of endometriosis and its associated symptoms. In particular, the alarmin, Interleukin (IL)-33 is elevated in the plasma, peritoneal fluid, and endometriotic lesions from endometriosis patients; however, the exact role of IL-33 in the pathophysiology of endometriosis is not well understood. In this study, we demonstrate, in both human patients and a murine model, that IL-33 contributes to the expansion of the novel group 2 innate lymphoid cells (ILC2s) and this IL-33 induced ILC2 expansion modulates the endometriosis lesion microenvironment. Importantly, we show that IL-33 drives hallmarks of severe endometriosis including elevated inflammation, lesion proliferation, and fibrosis and that this IL-33 induced aggravation is mediated by ILC2s. Finally, we demonstrate the functionality of IL-33 neutralization as a promising and novel therapeutic avenue for treating the debilitating symptoms of endometriosis.

Involvement of Atopic Dermatitis in the Development of Systemic Inflammatory Diseases

“…IL-33 also contributes to endometriosis development [ 49 ]. IL-33 levels increased the inflammatory response of endometriosis and developed the proliferation of endometrial cells mediated by group 2 innate lymphoid cells [ 49 ].…”

“…IL-33 also contributes to endometriosis development [ 49 ]. IL-33 levels increased the inflammatory response of endometriosis and developed the proliferation of endometrial cells mediated by group 2 innate lymphoid cells [ 49 ]. Consistently, IL-33-neutralizing antibody treatment impairs the inflammatory response in endometriosis [ 49 ].…”

Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells

“…Notably, IL-33 elevation is implicated in endometriosis and exogenous IL-33 exacerbates lesion severity and fibrosis dependent on ILC2s in a murine endometriosis model ( 325 ). Yet, in endometrial tissue of patients with endometriosis, ILC2s and ILC3s are reduced in abundance relative to non-endometriosis controls ( 326 ).…”

Tissue-resident immunity in the lung: a first-line defense at the environmental interface

“…As the innate counterpart of Th2 cells, ILC2s are involved in type 2 immunity, due to their ability to produce type 2 cytokines, such as IL-5, IL-4, and IL-13, upon stimulation by epithelial alarmins, including IL-33, IL-25, and thymic stromal lymphoprotein (TSLP) (Fig. 3) [38,53,54]. Hence, ILC2s play key roles in asthma and helminth infection [55,56].…”